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You may have heard the news; earlier this month an FDA committee unanimously concluded that phenylephrine, a common decongestant, doesn’t work. What does this mean? Why is it still on shelves? Is it poison? Should I throw my medicine away? Is the FDA a scam!? What’s the point of science if they change the rules?!?

We’ll address the last two questions first. Good science is a process of change. It’s not definitive; just our best, evidence-based guess at how to predict what will happen given current best experimentation and data. As we get more data of better quality the conclusions drawn by scientists change. To be clear, when scientists update their conclusions this is good and means science is working. It means we are getting more accurate information through better practices and updated information. New technology plays a big part in this. Think of it like maps. The first explorer to document an area may have a hand-drawn map outlining the major features. Later cartographers may come along and refine the map, making it more accurate and filling in the details. Their map may show a landmark in a different, more accurate position. This doesn’t mean the original mapmaker was malicious, or that maps don’t work, but instead that we can update our information to have a more accurate view of the world.

Back to the issue at hand, let’s find out what we’ve learned. On September 11th and 12th, 2023, the Non-prescription Drug Advisory Committee reviewed the results of several clinical studies which looked into the effectiveness of oral phenylephrine at lowering nasal congestion (stuffy nose). These studies measured symptoms in hundreds of patients who took phenylephrine and/or a placebo sugar pill in controlled environments. These studies found, by and large, that the decongestant was not significantly better than the placebo at providing relief. It should be noted that in the studies, most patients found relief from both phenylephrine and the placebo! It should also be noted that participants had few or no adverse reactions to the studies, though some had headaches. In response, the committee concluded that phenylephrine is not effective at providing relief when compared with a placebo; the drug doesn’t work.

So what does this mean for me? First, note that this is an advisory committee. They provide independent advice to the FDA, but do not make policy. In the near term nothing has changed. The FDA will likely take a while to make any policy changes and may have public input. Additionally, the clinical trials did not find the medication dangerous, just ineffective. This means phenylephrine isn’t dangerous at the recommended doses; you don’t need to throw it away (unless it’s expired!). It also means that a phase-out period will probably be slow, because there isn’t a danger to the public beyond wasting money on a medicine that works no better than a placebo.

Finally, how did this happen? How did a medication that doesn’t work get past the FDA? The answer is that while oral phenylephrine doesn’t seem to provide relief, inhaled phenylephrine continues to show effectiveness! When the oral form was approved in the 1970s, scientists thought around 30% of the medication would be absorbed in the gut. It has come to light that around 1% of the decongestant medication is actually available for our body to use when taken orally. From this, it follows that we would need to take much higher doses to get significant relief, which comes with increased side effects – including to the heart! On top of this is the completely fascinating finding in 2015 that placebos are getting better. A meta-study of several placebo-controlled clinical trials found that the effects of medications stayed the same, but the effect of placebos has been increasing over time! Some scientists believe this may be because we expect medications to do more, so the placebo is more effective! This means that when clinical trials are repeated, medications have a more difficult time showing effectiveness versus placebo. Think of our map-makers. That same landmark may have been perfectly mapped by cartographers, but tectonic plates can still cause it to slowly shift position. Lucky for us this means that new medicines brought to market are virtually guaranteed to be more effective than if they were introduced last century!

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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References:

Division of Nonprescription Drugs 1 (DNPD1), Division of Inflammation and Immune Pharmacology (DIIP), Office of Clinical Pharmacology (OCP), Division of Epidemiology II (DEPI-II). (September 11, 2023). Efficacy of Oral Phenylephrine as a Nasal Decongestant. U.S. Food & Drug Administration. https://www.fda.gov/media/171915/download

U.S. Food & Drug Administration. (September 14, 2023). FDA clarifies results of recent advisory committee meeting on oral phenylephrine. U.S. Food & Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine

Meltzer, E. O., Ratner, P. H., & McGraw, T. (2015). Oral phenylephrine HCl for nasal congestion in seasonal allergic rhinitis: a randomized, open-label, placebo-controlled study. The Journal of Allergy and Clinical Immunology: In Practice, 3(5), 702-708. https://pubmed.ncbi.nlm.nih.gov/26143019/

Meltzer, E. O., Ratner, P. H., & McGraw, T. (2016). Phenylephrine hydrochloride modified-release tablets for nasal congestion: a randomized, placebo-controlled trial in allergic rhinitis patients. Annals of Allergy, Asthma & Immunology, 116(1), 66-71. https://doi.org/10.1016/j.anai.2015.10.022

National Library of Medicine. (March 3, 2011). Safety Study Comparing Phenylephrine HCL Extended Release Tablets 30 mg and Placebo (Study CL2007-07)(P07529)(COMPLETED).  U.S. Department of Health and Human Services.ClinicalTrials.gov ID NCT00874120. https://clinicaltrials.gov/study/NCT00874120?tab=results

Tuttle, A. H., Tohyama, S., Ramsay, T., Kimmelman, J., Schweinhardt, P., Bennett, G. J., & Mogil, J. S. (2015). Increasing placebo responses over time in US clinical trials of neuropathic pain. Pain, 156(12), 2616-2626. https://doi.org/10.1097/j.pain.0000000000000333